The main objective of this research was to compare the efficacy and security of bisoprolol (B), a new cardioselective beta-blocker, that does not have intrinsic sympathomimetic activity, and metoprolol associated to hydrochlorothiazide (HCTZ), in the treatment of patients with mild to moderate hypertension. Sixty-two hypertensive patients (47 females and 15 males) aged 20 to 70 years (mean 52.5 +/- 10.4) were included in a double-blind, placebo controlled and randomized clinical trial. After a two-weeks wash out period and a similar placebo phase, patients were randomly assigned to receive either a once-daily dosing of B (10 mg) with 6.25 mg of HCTZ, or M (100 mg) plus 6.25 mg of HCTZ during four-weeks. If there was no reduction below 90 mmHg at the end of this period, the dosing of either beta-blocker was doubled. After eight weeks of treatment, the mean decreases in systolic/diastolic blood pressures from baseline were 31.8/21.2 and 28.0/20.6 mmHg for B/HCTZ and M/HCTZ, respectively (p < 0.0001). There were no clinically significant changes from baseline in laboratory parameters in either group. Reduction in blood pressure with B/HCTZ is associated with adverse events and metabolic changes similar to those observed with other antihypertensive drugs.